Many signal transduction pathways have been implicated in cancer, yet the exact mechanisms of how these pathways leads to cancer remain unknown. Mutations in the Wnt/beta-cat/TCF signaling pathway are associated with more than 90% of all colorectal cancer (CRC) cases. All these mutations result in aberrant activation of the pathway to promote tumorigenesis. By identifying and analyzing the target genes of this pathway, it will be possible to understand the molecular details of how activation of the Wnt signaling promotes tumorigenesis. In this proposed study, I plan to identify a set of genes directly regulated by the Wnt pathway in colorectal cancer cells using a novel genome-wide approach. Using these direct target genes, I will develop a general approach for diagnosis of abnormal signal pathways in cancer cells. To analyze the possible functions of each target genes in tumorigenesis, I will develop high throughput assays for functional analysis of identified target genes using siRNA. Results from these experiments will provide a detailed picture of how differential expression mediated by the Wnt/beta-cat/TCF pathway activation promotes the cancer phenotype.